The objectives of the proposed work are: 1) Develop a purification procedure which yields homogeneous preparations of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-CoA reductase). 2) Establish the purity of these enzyme preparations. 3) Characterize the homogeneous reductase preparations. 4) Utilize these preparations to distinguish between the various proposed mechanisms for the regulation of HMG-CoA reductase activity and cholesterol biosynthesis. During this past year, we have developed a procedure which consistently yields homogeneous preparations of HMG-CoA reductase.